Salud Brasil , São Paulo, Lunes, 02 de junio de 2014 a las 09:56

Natural products help in the treatment of intestinal inflammatory diseases

In experiments with rats, Brazilian researchers verified the beneficial effects of the “jatobá-do-cerrado” and the cattail

Diego Freire/Agência FAPESP /DICYT A study performed at the Institute of Biosciences of the Universidade Estadual Paulista (Unesp) in Botucatu (SP) has determined the effectiveness of natural products derived from Brazilian plants in treating inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn’s disease. The study also presents new molecular markers that may broaden the understanding of these diseases, whose etiology is yet unknown.

 

“We consider this a bold project because it studies not only the disease itself by prioritizing molecular targets of classic drug action but also the pharmacological targets of new products, such as natural coumarins and some medicinal plants,” said Luiz Claudio Di Stasi, the leader of the FAPESP-funded study, entitled “Inflammatory bowel disease (IBD): new molecular markers and intestinal anti-inflammatory activity of drugs and plant products.”

 

Among the principal findings is the discovery that a diet that includes green banana flour may prevent intestinal inflammation in rodents.

 

“We considered the importance of intestinal microbiota in protecting against the inflammatory process in order to propose a study of some of the natural products that could be added to one’s diet to offer the ability to modulate the intestinal microbiota ahead of time and to prevent the recurrent symptoms of ulcerative colitis and Crohn’s disease,” Di Stasi said.

 

The group led by the researcher studied several prebiotic agents – fibers that serve as “food” for beneficial intestinal bacteria, helping to balance the intestinal flora – such as polydextrose and fiber from the green dwarf banana (Musa spp. AAA), the jatobá-do-cerrado (Hymenaea stigonocarpa) and the cattail (Typha angustifolia).

 

Stem bark from the jatobá-do-cerrado and flour from the fruit pulp presented anti-inflammatory effects in rats with intestinal inflammation caused by trinitrobenzenesulfonic acid (TNBS). According to findings published in the Journal of Ethnopharmacology, “the pharmacological effects are related to the presence of antioxidant compounds in the extract, such as flavonoids, condensed tannins and terpenes, in the stem bark and fruit pulp of the jatobá-do-cerrado.”

 

The project also studied several concentrations of flour produced from the stalk of the cattail, a common Brazilian aquatic plant typically found in swamps, mangroves and floodplains. The healing effects of a diet that included 10% flour reduced the damage caused by IBD, in the form of adhesions of adjacent organs and diarrhea.

 

These effects are related to the inhibition of biochemical markers of colon inflammation, such as the activity of the enzyme myeloperoxidase, which is released in response to microbial invasions, and of alkaline phosphatase. This inhibition in turn inhibits the growth of intestinal bacteria that stimulate inflammation and prevents the translocation of microorganisms into the bloodstream, in addition to attenuating the activities of glutathione, a water-soluble antioxidant.

 

“The flour from the cattail stalk proved to be as effective as prednisolone, the anti-inflammatory steroid currently used to treat IBD, but without the adverse side effects,” said Di Stasi. Studies on the plant were described in an article published in BMC Complementary and Alternative Medicine.

 

In another group of experiments, the researchers studied various isolated natural coumarins, chief among which was 4-methylesculetin. This coumarin is the active ingredient in the leaves and roots of several species of plants, including those of the genus Mikania, which includes several plants popularly known as guaco in Brazil.

 

The research, published in the scientific journals Chemico-Biological Interactions and The European Journal of Inflammation, showed that 4-methylesculetin produces effects similar to prednisolone and that its protective effects are related to its ability to reduce oxidative stress in the colon and to inhibit the production of pro-inflammatory cytokines. According to the researchers, the administration of methylesculetin in the research models yielded preventive as well as curative effects.

 

New markers

 

Because the causes of IBD are not clear, greater knowledge of the mechanisms that regulate the integrity of the intestinal barrier and its function could help in understanding how medications currently used for its treatment work.

 

Therefore, the study also investigated how expression of the enzyme heparanase, the protein complex NF-kB, the hypoxanthine phosphoribosyl transferase (HPRT) gene, and the HSP70 protein affect the intestinal inflammation induced by TNBS in rats. Additionally, the anti-inflammatory effects of the allopathic sulfasalazine medicines prednisolone and azathioprine were examined, thus enabling an understanding of new modes of action of these drugs.

 

“Our findings indicate that heparanase, NF-kB, HSP70 and the HPRT gene are pharmacological targets that have to be considered in studies of new medicines to treat intestinal inflammation because they are important molecular targets that explain some of the etiopathogenic aspects of IBD,” explained Di Stasi.

 

The researchers now plan to study several species of food plants from the Amazon region as potential prebiotic products that can be used as fermentation substrates for beneficial intestinal flora, resulting in an increase in the amount of these bacteria and their metabolites, which have immunomodulatory and anti-inflammatory activity.

 

The idea, according to Di Stasi, is to enable the production of functional nutrients, “adding value to products that already have scientific and commercial appeal and expanding the possibilities for prevention by incorporating them into a diet that helps to prevent the recurrence of these diseases.”

 

The group also plans to study species studied in the past, along with those from Amazônia, to determine whether intestinal microflora as well as their metabolites are modulated. They additionally plan to conduct synergistic studies with drugs involving more promising species to identify new molecular targets, to obtain data that may further explain the etiology of IBD and to determine new treatment and prevention strategies.